When hepatitis B, C viruses (HBV and HCV respectively) persist in a chronic carrier state, they serve as a reservoir for infection and give rise to chronic hepatitis and cirrhosis that usually progress to hepatocellular carcinoma, one of the most common malignant tumors with an extremely poor prognosis. Currently approved treatments for chronic hepatitis B—interferon, lamivudin and adefovir—are limited by low rates of sustained response, side effects, or drug resistance. Managing patients with HCV infection consists primarily of antiviral treatment, currently with peginterferon and ribavirin.
IBDV has a worldwide distribution and can cause considerable damage to the poultry industry. IBDV is the causative agent of acute or immunosuppressive disease in chickens. Some zoonotic diseases are of continuing concern, however, IBDV is not known to be a hazard in transmitting to other species despite its worldwide distribution in the domestic fowl (Kibenge et al., 1988a); (Pedersden et al., 1990). IBDV is known to exert an inhibitory effect on the replication of hepatitis A virus in monkeys (Csatary et al., 1984). A bursa virus superinfection strategy has been tested for the treatment of acute B and C viral hepatitis in patients (Csatary et al., 1998). The use of IBDV as therapeutic agent in patients suffering from chronic hepatitis infections has also been reported (Bakacs and Mehrishi, 2002); (Csatary et al., 1999).
Given the hurdles associated with the development of anti HCV and HBV agents, there remains a need for improved therapy for both acute and chronic viral liver infections. This can be achieved by the use of IBDV vectors that have great flexibility in their construction and use, and can provide greater success in the treatment of viral liver diseases. An IBDV vector that can replicate in human liver cells without causing detrimental effects to them would be ideal. The present invention provides such vectors, and therapeutic methods involving the use of such vectors.